The purpose of this project is to gain insight into the genetic and biochemical basis determining human longevity. Our major research approach is an investigation of the molecular genetic basis of the substantial differences found in the aging rate observed in mammalian species. Research projects have centered on testing the dysdifferentiative hypothesis of aging. Here, recombinant DNA biotechnological methods are used to determine possible age-dependent alterations in gene regulation. Recent work has been centered on measuring possible age-dependent expression of endogenous retroviral genes. These include IAP genes in mice, MuLV-like genes in mice and humans and various oncogenic genes in mice and humans. Results suggest variation in expression with age that could contribute importantly to aging. Stability of the genome has been investigated by measuring total DNA 5-methylcytosine content in various tissue of Mus and Peromyscus species with age. Results have suggested a decease